Summary Vitamin C Physiology Rather than deficiency models, a concentration-function approach is a more rational method to determine vitamin intake recommendations for humans. At its heart, this approach relies on extensive and comprehensive characterization of vitamin physiology in healthy people. It is essential to have intensive and thorough datasets, as knowledge of normal physiology is a key to opening unexpected applications to health maintenance and disease treatment. Vitamin C is used as a model vitamin for this work. Physiology methodology, coupled to concentration-function relationships, also depends on understanding vitamin C biochemistry, molecular biology, and clinical pharmacokinetics. To study concentration-function and physiology relationships in humans for vitamin C, it is necessary to choose clinical samples that can be obtained easily; that contain the vitamin; and where changes in vitamin C concentration may affect physiology and/or cell function. For these reasons, one area of study is human red blood cells. As a prerequisite, we developed a new method to measure vitamin C in human red blood cells. This method is the foundation for exploring new functions of vitamin C in red blood cells in health and disease, with a major focus on diabetes. Humans, unlike most animals, cannot synthesize vitamin C and instead must obtain it from diet. Healthy humans who eat at least 5 servings of fruits and vegetables daily will obtain 200 mg or more of vitamin C. This will produce steady-state fasting plasma concentrations of 70 -80 moles per liter. Ingestion of more vitamin C from foods will not produce higher concentrations. Even if a vitamin C supplement is taken, plasma concentrations will only rise transiently. All tissues, except red cells, accumulate vitamin C against its plasma concentration. However, once plasma concentrations reach 50 to 60 moles per liter, tissue concentrations are saturated and do not rise further. Thus, vitamin C concentrations are tightly controlled. We study mechanisms of how vitamin C is tightly controlled in animals and humans, and consequences of aberrancies in these mechanisms. We also study mechanisms and consequences of paracrine, or local, release of vitamin C.